text: The stereochemical result of a given reaction on a macrocycle capable of adopting several conformations can be modeled by a Curtin-Hammett scenario.  In the diagram below, the two ground state conformations exist in an equilibrium, with some difference in their ground state energies. Conformation B is lower in energy than conformation A, and while possessing a similar energy barrier to its transition state in a hypothetical reaction, thus the product formed is predominantly product B (P B) arising from conformation B via transition state B (TS B).  The inherent preference of a ring to exist in one conformation over another provides a tool for stereoselective control of reactions by biasing the ring into a given configuration in the ground state.  The energy differences, ΔΔG and ΔG are significant considerations in this scenario.  The preference for one conformation over another can be characterized by ΔG, the free energy difference, which can, at some level, be estimated from conformational analysis. The free energy difference between the two transition states of each conformation on its path to product formation is given by ΔΔG. The value of ΔG between not just one, but many accessible conformations is the underlying energetic impetus for reactions occurring from the most stable ground state conformation and is the crux of the peripheral attack model outlined below.